QuantiFERON -TB Gold (QFT ) Tuberculosis Screening with QuantiFERON. Lunch and Learn. Cathy Yanda. Nancy Hyland



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QuantiFERON -TB Gold (QFT ) Tuberculosis Screening with QuantiFERON Lunch and Learn Cathy Yanda Corrections Specialist, QuantiFERON 312-504-2942 Nancy Hyland Inside Sales, QFN West 661-702-3752 US QFT Product Training QM31635261A Approval date 06/2013 1

Tuberculosis Background Disclaimer QuantiFERON -TB Gold (QFT ) is CE marked. QFT is approved by the US FDA. QFT is approved by the FDA as an in vitro diagnostic aid for detection of Mycobacterium tuberculosis infection. It uses a peptide cocktail simulating ESAT-6, CFP-10 and TB7.7(p4) proteins to stimulate cells in heparinized whole blood. Detection of IFN-γ by ELISA is used to identify in vitro responses to these peptide antigens that are associated with M. tuberculosis infection. FDA approval notes that QFT is an indirect test for M. tuberculosis infection (including disease) and is intended for use in conjunction with risk assessment, radiography and other medical and diagnostic evaluations. QFT Package Inserts, available in up to 25 different languages, can be found at www.quantiferon.com. US QFT Product Training QM31635261A Approval date 06/2013 2

QuantiFERON -TB Gold (QFT ) Technology Immunological basis of QFT US QFT Product Training QM31635261A Approval date 06/2013 3

Immunological Basis of QFT Modern TB diagnostics measure IFN-γ Adaptive immunity Humoral immunity B cells (antibodies) Cell-mediated immunity T cells (cytokines) IFN-γ is a marker of cell-mediated immunity (CMI) T cells produce IFN-γ when activated in response to antigen Secreted, measurable, stable Absent from normal circulation QFT stimulates CD4 + T cells Extensive literature showing importance of IFN-γ in TB infection US QFT Product Training QM31635261A Approval date 06/2013 4

Immunological Basis of QFT Measuring CMI is the key for a diagnostic test for LTBI Latent TB Infection Active TB Cell Mediated Immunity Immune Response Mycobacterial Load Infection Time Disease US QFT Product Training QM31635261A Approval date 06/2013 5

QFT Technology Summary QFT assay QuantiFERON-TB Gold (QFT) - whole blood indirect test to screen for tuberculosis (TB) infection Detects a cell-mediated immune response (CMI) to TB infection by measuring the IFN-γ from cell-mediated immune response to M. tuberculosis from CD4 + T cells QFT contains TB specific antigens which make it highly specific for TB infection Does not differentiate between latent TB infection and active disease QuantiFERON - TB Gold has significant advantages over TST in LTBI screening: More specific More accurate Does not cross-react with BCG-vaccination and most non-tuberculous (environmental) mycobacteria Requires single visit Not subject to human interpretation QFT is a modern and effective method for TB testing US QFT Product Training QM31635261A Approval date 06/2013 6

QuantiFERON -TB Gold Technical Performance QFT System Overview QFT Step-by-Step Test Procedure Interpretation of QFT Results QFT Performance Characteristics QFT on Automated Platforms US QFT Product Training QM31635261A Approval date 06/2013 7

QFT System Overview QFT blood collection tubes QFT ELISA* QuantiFERON supplies needed at the draw site QuantiFERON Tubes Nil, TB Antigen, and Mitogen tubes Incubator 37ºC ± 1ºC Centrifuge Available via the Texas TB Control Program *Enzyme-Linked Immunosorbent Assay US QFT Product Training QM31635261A Approval date 06/2013 8

QFT System Overview 3 blood collection tubes Nil (Grey cap) Negative control Adjusts for background noise or non-specific IFN-γ in blood samples TB Antigen (Red cap) Contains highly specific TB antigens: ESAT-6, CFP-10, TB7.7(p4) Mitogen (Purple cap) Positive control May indicate: - Decreased patient immune status, or - Incorrect blood handling & incubation US QFT Product Training QM31635261A Approval date 06/2013 9

QFT System Overview QFT Results Provides a qualitative result, which needs to be interpreted in conjunction with other clinical evaluations: Result Positive Negative Indeterminate Interpretation TB infection is likely TB infection is unlikely Results are indeterminate for TB Antigen responsiveness A quantitative result is also provided as additional information on your report. US QFT Product Training QM31635261A Approval date 06/2013 10

QuantiFERON -TB Gold Technical Performance QFT System Overview QFT Step-by-Step Test Procedure Interpretation of QFT Results QFT Performance Characteristics QFT on Automated Platforms US QFT Product Training QM31635261A Approval date 06/2013 11

QFT Step-By-Step Procedure Quick guide Step 1. Blood Collection Step 2. Mixing of Tubes Step 3. Incubation Step 4. ELISA* Step 5. Calculation of Results* * Both of these steps performed in laboratory and can be automated US QFT Product Training QM31635261A Approval date 06/2013 12

QFT Step-By-Step Procedure Blood collection into QFT tubes Tubes should be between 17ºC-25ºC at the time of blood filling Collect 1 ml by venipuncture into each tube as shown If a butterfly needle is used to collect blood, a purge tube should be used to fill tubing with blood and prevent tube underfill Hold tube on needle for 2 to 3 seconds after flow ceases as QFT tubes fill relatively slowly Take all three tubes and shake firmly up and down 10 times Hemolysis is expected and will not interfere with the test Standard blood handling precautions apply US QFT Product Training QM31635261A Approval date 06/2013 13

QFT Step-By-Step Procedure QFT Blood Collection Tips and Information QFT tubes use vacuum to draw blood and fills slowly wait extra 2-3 seconds Standard QFT blood collection tubes are validated to fill with 0.8 ml and 1.2 ml of blood Black mark on tube side indicates 1 ml fill volume If level of blood not close to the black mark, obtain another blood sample into a new tube Prior to incubation, maintain the tubes at room temperature (22 C ± 5 C) Do not refrigerate or freeze the blood samples Bi-monthly live webinar trainings are available 0.8 ml 1 ml 1.2 ml US QFT Product Training QM31635261A Approval date 06/2013 14

QuantiFERON -TB Gold Technical Performance QFT System Overview QFT Step-by-Step Test Procedure Interpretation of QFT Results QFT Performance Characteristics QFT on Automated Platforms US QFT Product Training QM31635261A Approval date 06/2013 15

QFT Performance Characteristics Predictive value of QFT Diel et al (1) 954 close contacts 198 QFT-positive 756 QFT-negative 142 QFT-positive/ TST-positive 5 QFT-positive TST-negative* 51 QFT-positive (49 TST-positive) 413 TST positive 343 TST negative Not treated Not treated Chemoprophylaxis RIF and/or INH Not treated Not treated 17 developed active TB 2 developed active TB No active TB No active TB No active TB 1. Diel, R.,et al. (2011) Am J Respir Crit Care Med 183, 88. US QFT Product Training QM31635261A Approval date 06/2013 16

Guidelines and Reimbursement Guidelines for TB screening in the US US QFT Product Training QM31635261A Approval date 06/2013 17

Guidelines for TB Screening in the US CDC guidelines (1) 1. Centers for Disease Control and Prevention (2010) MMWR 59:RR-5 US QFT Product Training QM31635261A Approval date 06/2013 18

Guidelines for TB Screening in the US CDC guidelines (1) IGRAs may be used in place of (and not in addition to) TST in all situations in which CDC recommends TST IGRA is preferred: For testing persons from groups that historically have poor rates of return for TST reading. For testing persons who have received BCG Of critical importance is the ability for a test to predict risk for subsequent active disease (remember PPV!) 1. Centers for Disease Control and Prevention (2010) MMWR 59:RR-5 US QFT Product Training QM31635261A Approval date 06/2013 19

QuantiFERON in Contact Investigations Qiagen Team Contact Information If you are interested in using the TBoss services for your next contact investigation please contact: For general QuantiFERON Information and Support: Cathy Yanda Cathy.Yanda@qiagen.com 312-504-2942 Nancy Hyland Nancy.Hyland@qiagen.com 661-702-3752 US QFT Product Training QM31635261A Approval date 06/2013 20